This program project is an integrated epidemiology laboratory investigation of current critical issues in tobacco-related cancers. The overall goal is to increase our knowledge of the etiology and prevention of tobacco-related cancers, and of the mechanisms of tobacco carcinogenesis. The program takes advantage of the unique expertise which the American Health Foundation possesses in the disciplines of tobacco epidemiology and tobacco carcinogenesis. The four projects are: 1) a continuation of our case-control study of tobacco-related cancers. 2) an investigation of hemoglobin adducts of tobacco specific nitrosamines (TSNA) as an index of risk for lung and oral cavity cancer. 3) a case-control study of tobacco-related cancers in Blacks to permit comparison with results from project 1. 4) a metabolic epidemiological study in Blacks and Whites to investigate the relationship between metabolic activation of tobacco carcinogens and will be administered by the Scientific Management Core, with data management support from the Biostatistics and Computer Core. Project 1. focuses on the impact of low-tar cigarettes on lung cancer histology, the risk of cancer associated with environmental tobacco smoke exposure, as well as other factors for tobacco related cancers such as family history of cancer, reproductive and menstrual cycle history and exogenous hormones and occupational exposures. Project 2 will determine the level of TSNA globin adduct in lung and oral cancer patients as well as determine factors which affect the level of these adducts. Project 3 is parallel to Project 1 in design and criteria, and will focus on risk factors for cancers of the lung, oral cavity, esophagus and bladder. Project 4 will use hemoglobin adducts of tobacco carcinogens and urinary metabolites related to carcinogen activation and detoxification to investigate mechanisms for the observed racial differences in cancer etiology.